The present study aimed to investigate whether microbial invasion of the amniotic cavity affects maternal plasma or placental immunoreactive corticotrophin releasing factor (ir-CRF) concentrations in pregnant women with pre-term or term labour. A cross-sectional study was conducted collecting blood samples in: (I) women with pre-term labour and intact membranes (25-36 weeks), with or without microbial invasion of the amniotic cavity (subdivided into three groups: IA, no microbial invasion of the amniotic cavity, delivery at term, n = 54; group IB, delivery < 48 h, no microbial invasion of the amniotic cavity, n = IO; group IC, delivery < 48 h, microbial invasion of the amniotic cavity, n = 8); (2) women at term, not in labour and without microbial invasion of the amniotic cavity (n = 15); (3) women in spontaneous active labour at term without (A) (n = 55) or with (B) (n = 16) microbial invasion of the amniotic cavity; and (4) healthy women not in labour at 25-36 weeks of gestation (n = 25). Specimens of trophoblast tissue were collected from pregnant women with pre-term labour (no microbial invasion of the amniotic cavity, n = 6; microbial invasion of the amniotic cavity, n = 4) or delivering at term (no microbial invasion of the amniotic cavity, n = 8; microbial invasion of the amniotic cavity, n = 4). A specific radioimmunoassay on acidic extracts of plasma or placental specimens was used. Patients with pre-term labour showed higher plasma ir-CRF concentration than healthy women at the same gestational age or at term not in labour, and those with microbial invasion of the amniotic cavity, had higher plasma ir-CRF concentrations than the ones without microbial invasion of the amniotic cavity (P < 0.05). Term labour was associated with elevated plasma ir-CRF concentrations, not affected by, the presence or absence of microbial invasion of the amniotic cavity. Placental ir-CRF concentrations in women with pre-term labour, in absence of microbial invasion of the amniotic cavity, mere significantly lower than in women with pre-term labour associated with microbial invasion of the amniotic cavity (P < 0.05). These findings showing a different pattern of maternal and placenta ir-CRF concentrations between pre-term labour with ol without microbial invasion of the amniotic cavity, support the hypothesis of an impact of infection on neuroendocrine activity, of human placenta.